Module for an analysis device, applicator as an exchange part of the analysis device and analysis device associated therewith

ABSTRACT

An analysis device that may be used in biochemical analyses includes a module in a first housing, including a chip support, a sensor chip and electrical contacts between the chip and the chip support. The chip is encapsulated so that the electrical contacts are insulated and the sensitive surface of the sensor chip remains accessible to a fluid to be tested. The module and the first housing form an exchangeable applicator or chip card with mocrofluidic components or functions and is inserted into a second housing that has an evaluation unit for reading and analyzing measured data.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is based on and hereby claims priority to GermanApplication No. 101 11 458.3 filed on Mar. 9, 2001, the contents ofwhich are hereby incorporated by reference. This application is relatedto ANALYSIS DEVICE, filed concurrently by Walter Gumbrecht and ManfredStanzel and incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a module for an analysis device, in particularfor decentralized biochemical analytics, with a sensor chip in a firsthousing. In addition, the invention also relates to an applicator as anexchangeable part of the analysis device and to the associated analysisdevice.

2. Description of the Related Art

Microsensor technology and microsystems engineering have undergone adramatic development in the last 20 years on the technological platformof microelectronics. All technical-scientific disciplines have madetheir respective contributions to this and created a broad spectrum ofsensors and systems between physics and microbiology.

However, while physical concepts, such as for example pressure andacceleration sensors/systems, have gone through the process ofimplementation in terms of technical production and successfulintroduction on the market, most chemical-biological developments havenot got beyond the laboratory trial stage. This has been significantlyinfluenced by the fact that chemical-biological systems requiremicrofluidic components which, by definition, are not compatible withmicroelectronics in the first place, since the classic microelectroniccomponents are hermetically enclosed in a housing in order to avoid“material” contact with the surroundings. So it is that virtually allchemical-biological sensors/sensor systems are dependent on thedevelopment of a special housing technique.

There are a few cases in which microelectronic-compatible housingsolutions have been developed to the stage of introduction on themarket, for example ati-STAT Corporation, 303A College Road East,Princeton, N.J. 08540. Such a device is described in U.S. Pat. No.5,096,669 A: one or more Si chips have sensitive areas with chemicalsensors and contact areas for electrical connection to the reader. Thechips are mounted in a housing in such a way that large parts of thechip areas are used for sealing a throughflow channel, and large contactareas for electrical contacting are accessible from outside the housing.Consequently, a large part of the valuable Si chip area is wasted. Whatis more, the electrical contacting in the housing is located on the sameside as the sensitive areas of the chip, which makes it more difficultfor the electrical contacting to be reliably separated from thefluidics.

Furthermore, in Dirks, G. et al. “Development of a disposable biosensorchipcard system”, Sens. Technol. Neth., Proc. Dutch Sens. Conf, 3rd(1988), pages 207 to 212, there is a description of a measuring systemfor biomedical applications in which a so-called chip card is made froma flat container with a number of cavities and a system of fluidchannels, with an ISFET which serves as a sensor being introduced intothe channel system. In the case of this system, it is in particular amatter of separately feeding a measuring fluid on the one hand and acalibrating or reagent fluid on the other hand to the sensor fromseparate containers. Furthermore, in the monograph by Langereis, G. R.“An integrated sensor system for monitoring washing process”, ISBN 90,there is a description of systems with sensors concerned withintegrating in fluidic devices sensors which have their signalselectrically tapped. On account of the high development and productioncosts for comparatively low numbers of units of chemical-biologicalsystems, market penetration of these products is problematical.

SUMMARY OF THE INVENTION

An object of the invention is therefore to propose improvements by whicha successful introduction on the market appears possible in the case ofthe above devices.

In the case of a module according to the invention, it is particularlyadvantageous that the chip carrier is thin and has a thickness of <100μm. With thicknesses of about 50 μm of metal in combination with about100 μm of plastic, a considerable volume/material saving is obtained. Onaccount of the thin formation of the chip carrier and suitable material,such as for example gold-coated copper layers, only small masses, andconsequently low heat capacities, are obtained, so that, in combinationwith the good thermal conductivity of silicon and for example acopper/gold layer about 50 μm thick, a very good dynamic thermalbehavior results. The processing of the chip carrier takes place on astrip which is transported from reel to reel (“reel to reel” process),it being advantageously possible for the electrical contacting points tobe arranged on the rear side.

For the encapsulation of the chip carrier in the module, both materialsknown from microelectronics and materials with special properties, suchas for example elastic polymers, may be used. Bonding wires, which forma flat loop, are present, it being possible for the contacts for thebonding wires to be arranged in the region of the corners of the chips.

Following mounting, wire bonding and encapsulation of the chips on thestrip, the sensitive areas of the chips may be coated withchemical/biochemical substances, advantageously from the liquid phase,by a “reel to reel” technique. The encapsulation of the individualmodule in combination with the associated applicator producesparticularly favorable properties.

With a module according to the invention, a system which is suitable inparticular for decentralized applications can be created. With thecompact first housing, the module realizes an applicator as a measuringunit which can be used in a decentralized manner. For carrying out theanalysis and for reading out the measured values, the applicator can beintroduced into a second housing with an evaluation unit.

In the case of the invention, the applicator with the first housing andthe module integrated in it is advantageously formed in the manner of achip card. Together with the second housing, such a chip card can forman analysis device which can be used in a variety of ways. Inparticular, an analysis device of this type can be used for thescreening of body fluids, for example for decentralized blood gasmeasurements or saliva examinations. However, other applications inbiochemical analytics can also be realized.

A further advantageous application possibility of the invention is theamplification of DNA/RNA (deoxyribonucleic acid/ribonucleic acid)samples by the exponential replication method with the so-called PCR(Polymer Chain Reaction), i.e. the so-called polymerase chain reactionmethod. For this purpose, the sample fluid must be cycled 20 to 40 timesbetween two temperatures, typically between 40° C. and 95° C. In thecase of this method, the speed of the cycling operations is decisive. Asknown in the art, the cooling process is speed-determining.

For practical purposes, a particularly advantageous embodiment, that isthe chip card, comes into consideration as the applicator. In the caseof the chip card, the Si chip is mounted on the carrier, which—asalready mentioned—is made from a gold-coated copper layer onlyapproximately 50 μm thick. This is the middle metal zone of known chipcard modules, which is not used there for electrical contacting pointsin the card reader. This free zone can consequently be used in the cardreader, which serves as an evaluation device, for contacting inparticular a cooling element, for example a Peltier cooler, to thecorresponding location of the chip card. On account of the placement ofthe 50 μm thick metallic contact with respect to the chip, an efficientheat transfer is consequently possible, so that a defined temperaturecan be set very quickly.

It is particularly advantageous in the case of the invention that thehousing concept for realizing the microfluidics is based as much aspossible on those of classic microelectronics. This creates the mainprerequisites that allow modules with chemical-biological sensors orsensor systems of this type to have commercial success even in the caseof relatively small numbers of units.

Apart from the latter advantages, in the case of the invention it isalso taken into consideration that the chemical-biological sensor systemcan in particular also be used for once-only use, i.e. as a so-calleddisposable. Such systems are increasingly being adopted in practice.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects and advantages of the present invention willbecome more apparent and more readily appreciated from the followingdescription of the preferred embodiments, taken in conjunction with theaccompanying drawings of which:

FIG. 1 is a cross section through a chip module with wire bondingtechnology,

FIG. 2 is a cross section through a chip module with flip-chiptechnology,

FIG. 3 is a plan view of a chip card contacting zone with individualcontacting points,

FIG. 4 is a plan view of the chip sensor with the sensitive area,

FIG. 4A is an enlarged plan view of the exposed sensitive area of thechip in FIG. 4 when the sensor is used for biochemical applications,

FIG. 5 is a cross section with a more detailed representation to scaleof a chip card for the installation of a module with wire bondingtechnology,

FIG. 6 is a partial cross section corresponding to FIG. 5 for theinstallation of a module with flip-chip technology and reusablethrough-flow coupling,

FIG. 7 is a cross section of a combination of a module and an applicatorfor pushing into a reader and

FIG. 8 is a plan view from above and/or a cross section of the systemillustrated in FIG. 7.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Reference will now be made in detail to the preferred embodiments of thepresent invention, examples of which are illustrated in the accompanyingdrawings, wherein like reference numerals refer to like elementsthroughout.

The drawings, in particular FIGS. 1 and 2, are partly describedtogether.

Chip card technology is a known, widespread and extremely low-costhousing concept in microelectronics. In this case, a microsilicon chip,which has previously being ground thin to about 180 μm at wafer level,is adhesively attached to a carrier strip, which may be a gold-coated,pre-punched copper strip and is possibly reinforced with a strip ofplastic. After standard wire bonding, the chip together with the wiresis encapsulated in a polymer. A commercially obtainable standard plasticcard (materials: PVC, PET, PC; dimensions: about 85×54×0.8 mm³) ismilled out at a defined location to module size (about 13×12×0.4 mm³)for receiving the chip carrier module, so that once the module has beenpunched out of the carrier strip it can be adhesively bonded into themilled-out recess.

In FIG. 1, a chip module 15 with a sensor chip 1 in wire bondingtechnology is schematically represented. The module includes the actualchip 1 with a sensitive area 2 on the upper side, the chip 1 having beenapplied on the rear side of a carrier strip 3 of copper, which ifappropriate is gold-coated. On the carrier strip 3 with area-likecontact regions 3′, 3″, . . . there are elements 4 of plastic, which inparticular mechanically hold together the insulated contacting areas 3′,3″, . . . . Silicon microchips, such as for example microcontrollers ordata memories, have in the past already been mass-produced in a similarformation, so that they are extremely inexpensive.

In the case of the chip module 15 constructed in FIG. 1, there is anencapsulation 5, in which bonding wires 6, 6′, . . . for the contactingof the chip 1 are cast in. While previously a closed surrounding ofplastic covering the entire chip was provided by a so-called “glob top”,now the encapsulation 5 is formed flat with at least approximately aplanar surface and opening, since the entire module 15 is to beintroduced for example into a chip card as the housing.

In order to ensure complete wetting of the sensitive chip area 2 underoperating conditions of the analysis device, i.e. to avoid the inclusionof air bubbles during filling with fluids, it is important that theratio of the height of the encapsulation above the upper edge of thechip 1 to the diameter of the sensitive area of the chip 1 does notexceed approximately 1:5 and is typically less than 200 μm. As revealedby FIG. 5, which is to scale, 100 μm is an advantageous height for theencapsulation above the upper edge of the chip 1. In order to seal theflow channels, for example the inflow and outflow channels 12, 13 inFIG. 5, reliably with respect to the first housing, the encapsulation 5must have a defined lateral extent. A widening of the lateral extent ofthe encapsulation is necessary inter alia if the inflow and outflow areto lie outside the sensitive area of the chip 1, in order for example toavoid disturbing influences of an inhomogeneous flow of the fluids. Theinflow and outflow then meet the sensor module in the region of theencapsulation and can be reliably sealed there.

In a particular embodiment, the encapsulation 5 has a diameter of 10 mmand a clearance for the sensitive area 2 of the chip of 3 mm. Incombination with the ratio described above of the height of theencapsulation to the diameter of the sensitive area 2, a uniform flow ofthe fluids onto the sensitive area 2, i.e. parallel to the sensitivearea of the chip, is made possible.

The sensitive area 2 of the chip is preferably formed in a round manner.The delimitation of the sensitive area 2 with respect to theencapsulation 5 can be realized for example by a photostructured polymerring, as described further below in FIG. 6 as a PI (polyimide) ring 27.

In order to maximize the ratio of the sensitive area 2 to the overallarea of the chip 1, the form of the chip 1 is preferably approximatelyor exactly square, the electrical contacts of the chip 1 as so-calledbonding pads 2′ to 2 ^(VII) being located in the region of the chipcorners, so that the sensitive area can be made to extend up to the chipedges, which is revealed in FIG. 4. With a thickness of themetallization of the carrier strip of 50 μm, a chip thickness of 180 μmand height of the encapsulation above the chip 1 of 100 μm, an overallthickness of the module of approximately 330 μm is obtained.Consequently, the known chip module structures and dimensions frommicroelectronics are transferred to biochemical analytics, which is nota trivial matter on account of the necessary coupling of the fluidics.

In the case of an alternative to FIG. 1, according to FIG. 2 the chip 1is oriented with its sensitive area 2 downward. The sensor chip 1 isarranged in so-called flip-chip technology with a number of bump-likecontacts 8, 8′, . . . on the carrier strip 3 with its contact regions 3^(I), 3 ^(II), . . . , 3 ^(VIII), the carrier strip formed of copper, ifappropriate with a gold coating, in a form corresponding to FIG. 1.Insulating elements 4 are in turn present as mechanical connections ofelectrically insulating plastic, a clearance for the sensitive area 2 ofthe sensor chip 1 being present. Altogether, a chip module 15′ is formedin FIG. 2.

The operating principle of the chip module 15 or 15′, and in particularof the actual chip 1, is illustrated by the views from two sides of themodule on the basis of FIGS. 3 and 4. On the electrical contact side 3,i.e. the rear side, of the module 15 with the sensor chip 1, contactingzones 3 ^(I), . . . , 3 ^(VIII) can be seen as individual terminals,which correspond to the customary contacting points for chips which canbe integrated into a card. On the sensitive side 2 of the chip 1,according to FIG. 4 the wire bonds 6, 6′, . . . of the bonding pads 2^(I) to 2 ^(VII) run from the corners of the chip 1 to the contacts ofthe contacting zones 3 ^(I), . . . 3 ^(VIII). It is evident that herespecifically there are seven contacts 2 ^(I), . . . 2 ^(VII) on the chiparea 2, which is sufficient for many applications and is described belowfor an example.

In FIG. 4A, a multiplicity of microcavities 200 for carrying outbiochemical analyses are arranged on the sensitive area 2 of the chip 1.Such a system is described for example in the earlier German patentapplication with the application number 100 58 394.6-52, to whichreference is expressly made, and serves for carrying out biochemicalmeasurements, for example DNA analysis. There are m×n elements arrangedin the form of an array as a multiplicity of cavities 200 in the form ofrows and columns. The important aspect of this is that biochemicalreactions or measurements can take place simultaneously in theindividual cavities 200 on the sensitive surface of the single chip 1,without reactions from a first cavity 200 being able to disturb a secondcavity 200′ when substances are added.

Since in the case of a system according to FIGS. 4 and 4A theelectrochemical reactions electrically influenced or takes place byinquiring electrical signals, discrete electrical contacting points,which are designated by 3 ^(I) to 3 ^(VII), have been attached on thechip 1 with a sensitive surface 2 or the individual sensitive elements200. The contacting points form inputs for the electrical measuringcircuit. For example there are two supply voltage inputs V_(dd), V_(ss),an input GND for ground potential, an input for a clock signal, an inputV_(in) for a control voltage and an input for a reset signal.Furthermore, a multiplexer 210, a “Gray counter & decoder” 215 and anamplifier 220 are integrated on the chip 1 by a standard silicontechnique. The measuring signal is sensed at the ‘out’ output, with amultiplex signal which is read out for example at a frequency of 10 kHzbeing obtained in the case of an array system with the multiplicity ofcavities as m×n individual sensors.

The multiplex signal output on a single ‘out’ line includes a pattern ofdiscrete voltage values, from which the signals of the individual sensorare obtained by a demultiplexer in an evaluation device. Thedemultiplexer, not represented in FIG. 4A, is arranged for example inthe housing 80 of FIG. 7 or FIG. 8.

In another system, instead of a multiplicity of identical sensors, suchas the m×n cavities 200 corresponding to FIG. 4A, there may also bediscrete sensors. Specifically for applications in biomedicaltechnology, such sensors may be, for example, sensors for pO₂ and pCO₂.

Further sensors may also be combined with these. The eight contact zonesavailable in the case of the system according to FIG. 3 are generallyadequate for signal supply and signal removal. By dividing theelectrical contacting and fluid access between opposite sides of thesensor module 15, by contrast with U.S. Pat. No. 5,096,669 A a reliableseparation of the electrical contacting from the fluidics is ensured.Furthermore, unproblematical fluid access to the sensor module is madepossible. A circular planar surface 100 of the encapsulation 5 ofplastic with an advantageously inner round clearance 101 on the chip 1achieves the effect of reliable insulation of the wire bondingcontacting points 6, 6′ and equally keeps the sensitive chip area 2centrally free.

The production of the sensor modules takes place in a so-called “reel toreel” process as known technology on a flexible basic body. In the “reelto reel” process, a carrier strip is processed, i.e. the operations a)adhesive chip attachment, b) wire bonding/flip-chip, c) encapsulationare processed in an automated manner from film reel to film reel—whichin mass production can take place on a conveyor belt—up to the finishedmodule. Subsequently, the modules are punched out and installed in aclose-fitting manner into the “first housings”.

In FIGS. 5 and 6, the two alternative systems of modules introduced in afirst housing are represented, with wire-bonding technology on the onehand and flip-chip technology on the other hand. In both cases, thesystem respectively includes substantially a standard plastic card 10 or20 with microfluidic components and functions, which will be discussedin more detail further below. Especially the card 10 may have additionallayers 18, for example an adhesive film or the like, with which theentire unit is sealed against environmental influences.

In the card 10 according to FIG. 5, a microchannel 11 and inflow/outflowchannels 12 and 13 are present as microfluidic components, which serveinter alia for transporting substances and/or reagents. What isimportant is a clearance 14 in the housing 10, into which the chipmodule 15 according to FIG. 1 or FIG. 2 is introduced in suitablepositioning. The clearance 14 must be adapted to the encapsulation 5 ofthe chip 1. In this case, a radial symmetry with an axis perpendicularto the active area of the chip 1 and/or a planar encapsulation parallelto the active area of the chip 1 may be advantageous.

During the mounting of the module 15 into the clearance 14 of the firsthousing 10, a fluid-tight connection must be ensured between the surfaceof the encapsulation 5 and a layer 19 of a material which carriesmicrofluidic components, such as the inlet 12 and outlet 13. This may beachieved by adding auxiliary means such as adhesives or double-sidedadhesive tapes 17. In a particularly advantageous embodiment, it ispossible to dispense with the auxiliary means by using an elasticencapsulating material 5. During the operation of the analysis device,the elastic encapsulation 5 is pressed onto the material of the layer 19which is carrying the microfluidic elements of the first housing 10, sothat the channel 11 with the inlet 12 and the outlet 13 are sealed. Thepressing may take place for example by an actuator in the secondhousing.

The entire chip module 15 or 15′ corresponding to the alternativesaccording to FIG. 1 or FIG. 2, including the silicon chip 1 with thesensitive area 2, is consequently inserted into the basic body, inparticular the card body 10 in FIG. 5, in such a way that the system isadequately sealed with respect to the outside, allows an inflow or entryof substances to be analyzed and only the active area of the chip 1 cancome into interaction with the substances to be analyzed. In order toensure complete wetting of the sensitive chip area 2 during operation,i.e. to avoid the inclusion of air bubbles, in particular in the channel11, it is important that the ratio of the height of the gap in themicrochannel 11 between the chip 1 and the layer 19 which is carryingthe channels with inlets and outlets 12, 13 to the diameter of thesensitive area 2 of the chip 1 is less than 1:5 or the gap 11 istypically smaller than 200 μm.

The specified gap of smaller than 200 μm is of advantage in the case ofdiffusion-controlled reactions, for example DNA hybridizing, on thesensitive area 2 of the chip 1. By making the co-reactants, which arefor example dissolved in the sample fluid, flow in a thin layer over thereactive, sensitive chip area 2, they can be offered in higherconcentration on the surface of the chip 1 in comparison with diffusionalone, which leads to speeding up of the reaction.

Represented in FIG. 6 as an alternative to FIG. 5 is a system whichincludes a card body 20 without internal fluidic components and in thiscase also without electrical functions. The chip 1 is contacted onto thecard body 20 with the sensitive area 2 oriented upward.

As a departure from FIG. 5, in FIG. 6 a partially “reusable” flow cellis used. The electrical inquiry and also the supply and removal ofsample fluids takes place from the outside. In the same way, of course,the chip module 15 according to FIG. 1 may also be operated with areusable flow cell, but then however with advantageous electricalcontacting on the rear side.

In FIG. 6, the card body 20 forms the first housing, with the measuringand analyzing function being realized in the upper part as a secondhousing. The fluidic and electrical components can be found in the upperpart.

In FIG. 6, the upper part 25, which is the carrier of inflow and outflowchannels 22 and 23, is mounted on the basic body 20, which together withthe module realizes the chip card as an applicator, in such a way that aso-called contact head is formed. The upper part 25 as the contact headhas resiliently mountable electrical contacts 26 and sealing means, suchas for example a sealing ring 24, are also present. The sealing ring 24serves for ensuring the tightness of the seal in the fluidic region 21between the upper part and the sensitive area 2 of the chip 1 with theresiliently mounted contacts 26 of the contact head 25 for theelectrical contacting through the chip 1.

In the applicator 20 of FIG. 6, by analogy with FIG. 5, the moduleaccording to FIG. 2 has been fitted with the silicon chip 1, thesensitive chip area 2 again being shown upward even with the flip-chiptechnology applied here—by contrast with FIG. 2, for the purpose ofillustrating the principle of flip-chip technology. The sensor chip 1including the carrier has in this case been fitted in the card body 20.

Further auxiliary components of flip-chip technology are present for thelatter purpose, such as for example a PI ring 27, a so-called underfill29 and a so-called bump 28, for sealing and maintaining the dimensionalstability of the chip position. These auxiliary components have provensuccessful in semiconductor technology and ensure the required qualityduring the manufacture of the sensor chips, in particular when thefluidics on the sensor area are to be managed.

The essential aspect in the case of FIG. 6 in the present connection isthat the separate upper part 21 only has to be mounted onto the basicbody 20 for measurement, and then, in this applied state, equallyensures on the one hand the fluidic connection and on the other hand theelectrical contacting at the existing through-contacting holes.

The card 10 according to FIG. 5 and the body 20 according to FIG. 6consequently form in each case a separately exchangeable, flatapplicator with a first housings for the respective measuring modules.For analysis and for reading out the measuring signals, theseapplicators with the first housing are pushed into a second housing ineach case, which is for example part of a stationary measuring andanalysis device or else may be a portable device for measuringactivities in changing locations.

Represented in FIGS. 7 and 8 is an applicator, having a sensor module 15and a first housing 60, which has been pushed into a second housing 80for carrying out the measurement and for reading out the measuredvalues. The sensor module 15, described in detail on the basis of FIGS.1, 4, 4A, has its functional area facing a fluid channel 11, into whichmeasuring and reagent solutions are introduced via a channel 110. Thereagent solution is produced in situ from pre-portioned solid reagents16, 16′, 16″ with a solvent fed in via an inlet 12. The measuring andreagent solutions pass via an outlet 13 to the second housing 80 for thepurpose of disposal.

The latter system is substantially the subject of a parallel applicationwith the same priority date (German patent application number 101 11457.5-52 of Mar. 9, 2001), to the disclosure of which reference isexpressly made.

In FIG. 7, a Peltier element 30 for thermostatic control, in particularcooling, of the chip area is assigned to the sensor module 15 withassociated contacts on the rear side in the second housing 80, so thatit is possible to operate at defined temperatures or rapid heat removalis ensured in cooling processes from high temperatures, for example 90°C., to lower temperatures, for example 30° C. On account of thematerials with very good heat conductivity, silicon and copper/gold, butalso the low layer thicknesses (about 180 μm of silicon; 50 μm ofcopper/gold), an outstanding heat transfer is ensured. For the Peltierelement 30, a cooling plate 31 is provided and, furthermore, electricalclamping contacts 33 are provided for the reading out of the chipinformation. By pressing the Peltier element 30 against the sensormodule 15, apart from improving the heat transfer, the sealing describedin detail above of an elastic encapsulation 5 of the module 15 to thematerial of the layer 19 carrying the microfluidic channels can takeplace.

The latter system can be used advantageously for the amplification ofDNA/RNA (deoxyribonucleic acid/ribonucleic acid) by an exponentialreplication method, the so-called PCR (Polymer Chain Reaction). For thispurpose, the DNA/RNA sample and required reagents, such as for examplenucleotide triphosphates, primary DNA/RNA andpolymerase/polymerase+reverse transcriptase in buffer solution are fedto the sensitive area of the sensor chip via the microfluidic channels.The immobilization of the DNA/RNA sample on the sensitive area of thechip is particularly advantageous here. This can take place for exampleby hybridizing on complementary capture DNA, which is bound on the chip,for example in the form of arrays. The reaction space, i.e. the spaceover the sensitive area of the chip with a height of up to severalhundred μm, is then cycled approximately 20 to 40 times between twotemperatures, typically between 40° C. and 95° C. In the case of thissystem, the entire DNA/RNA replication process can be carried out in afew minutes.

According to FIG. 8, a first reagent channel 61, which is connected to awater inlet 62, is present for the latter purpose in the first housing60. Furthermore, there is a second reagent channel 61′, which runsparallel to the first reagent channel 61 and, by contrast with thereagent channel 61, is not filled in the representation of FIG. 7. Thesecond reagent channel 61′ can be connected to a second water inlet 62′.Further parallel-connected reagent channels 61″, . . . may be provided,with water inlets 62″, . . . , which are respectivelyparallel-connected, so that altogether n reagent channels and n waterinlets are formed. Furthermore, there is an input port 68 for the fluidwhich is to be examined, for which the measurement sample is transportedvia a channel 69 to the sensor module 15, without previously having tocome into contact with the reagent fluid. Finally, an outlet 63 isprovided, via which the fluid is discharged after flowing past thesensitive area 2 of the sensor module 15.

Alternatively, the used fluids may remain in a corresponding volume, forexample by widening of the channel or lengthening of the channel in theform of a meander, of the first housing. In the reader of the secondhousing 80, a water distribution system with valves is provided.

The described example of an analysis device with chip cards which can bepushed into a reader as measuring applicators consequently makes use ofthe main components and of previous chip card technology. For theoperating principle of a chip card with combined electrical and fluidiccomponents, the following main, non-trivial changes or additionalfeatures are provided:

A modified encapsulation of the chip and of the electrical contacts viabonding wires ensures that only the chemical-biologically active area ofthe chip remains free from the encapsulation.

The modified encapsulation of the sensor chip and of the associatedbonding wires has a defined geometry.

The encapsulation has a defined thickness, a defined lateral extent andalso an at least approximately planar and/or radially symmetricalsurface for the exact insertion of the sensor chip into a chip card.

To sum up, the following should also be emphasized in addition to theabove examples with respect to the use of chip card technology inchemical-biological measurement: in all the embodiments, theconfiguration of the system including the chip card with the functionalvolume takes place in such a way that microfluidic components andfunctions are integrated in the interior and/or on the surface of thecard. This makes it possible for liquids or gases to enter the chip cardand be transported in the interior or on the surface of the chip cardand be available in the region of the silicon chip of the active area ofthe chip. This is where the measurement takes place, after which theliquids or gases in the region of the silicon chip can subsequently becarried away from the active area of the chip and leave the chip card.If appropriate, substances can be stored in the interior or on thesurface of the chip card or remain there after use.

An important aspect is the clearance in the chip card for receiving thechip module in such a way that a reliable microfluidic connection ismade possible between fluid channels of the plastic card and the active,i.e. sensitive, area of the chip and no external influences can disturbthe measurement.

Dependent on the required position of the microfluidic components, thechip card may include one or more components or layers, which are joinedtogether by known connecting methods, such as adhesive bonding, welding,laminating or the like.

The components for the microfluidic functions may be produced by a widevariety of methods, such as milling, punching, stamping,injection-molding, laser ablation or the like.

On account of certain requirements, for example with respect to thechemical resistance or the thermal endurance, the applicator itself maybe made of a wide variety of materials and consequently be adapted tothe requirements in the particular instance.

It is possible to the greatest extent to rely for this purpose on theknow-how of card technology.

This consequently provides an analysis device which, apart from inbiochemical analytics, can also be used in a variety of ways, inparticular for use in medical diagnostics, forensics, for foodmonitoring and for environmental measuring technology. The decentralizeduse of the applicator and reader allows time-saving low-cost examinationon the spot, in particular in clinics and doctors' own practices, of forexample blood, liquor, saliva and smears, for example for viruses ofinfectious diseases. This may include, if necessary, not only simpletyping of the germs, but also for example the determination of anyresistances to antibiotics, which significantly improves the quality ofthe therapy and consequently can reduce the duration and cost of theillness.

Apart from the diagnosis of infectious diseases, the diagnosis system isfor example also suitable in medicine for blood gas/blood electrolyteanalysis, for therapy control, for early detection of cancer and for thedetermination of genetic predispositions.

For all the intended uses specified, the applicator may be formed as anautonomous unit, in which a voltage source, simplified evaluationelectronics and a display are present in the applicator housing.

The invention has been described in detail with particular reference topreferred embodiments thereof and examples, but it will be understoodthat variations and modifications can be effected within the spirit andscope of the invention.

1-34. (canceled)
 35. A module for a decentralized biochemical analysisdevice, comprising: a sensor chip having a sensitive area and electricalcontacts; and a carrier having contact zones associated with theelectrical contacts of said sensor chip and an encapsulation withcontact connection between the contact zones and the electrical contactsof said sensor chip to provide electrical access from outside saidmodule, the encapsulation allowing access by a fluid to the sensitivearea of said sensor chip.
 36. The module as claimed in claim 35, whereina ratio of height of the encapsulation above an upper edge of saidsensor chip to a largest diameter of the sensitive area of said sensorchip is less than 1 to
 5. 37. The module as claimed in claim 35, whereinthe encapsulation of said sensor chip has a defined lateral extent toseal fluidic inflow and outflow.
 38. The module as claimed in claim 35,wherein the encapsulation includes an elastic material, whereby thefluidic inflow and fluid outflow can be sealed without aid of furthermeans.
 39. The module as claimed in claim 35, wherein the electricalcontacts of said sensor chip are bonding pads in corners of said sensorchip.
 40. The module as claimed in claim 36, wherein the encapsulationhas at least one of a substantially planar surface and a radiallysymmetrical surface.
 41. The module as claimed in claim 40, wherein saidmodule is a chip card.
 42. The module as claimed in claim 35, whereinsaid carrier is a metallic carrier strip having a thickness of less than100 μm and the contact zones are plastic-reinforced metal contacts. 43.The module as claimed in claim 42, wherein said sensor chip is mountedon the metallic carrier strip by wire bonding.
 44. The module as claimedin claim 42, wherein said sensor chip is mounted on the carrier strip asa flip-chip.
 45. An applicator as an exchangeable part of an analysisdevice, comprising: a first housing, including a module, including asensor chip having a sensitive area and electrical contacts; and acarrier having contact zones associated with the electrical contacts ofsaid sensor chip and an encapsulation with contact connection betweenthe contact zones and the electrical contacts of said sensor chip toprovide electrical access from outside said module, the encapsulationallowing access by a fluid to the sensitive area of said sensor chip;and means for inflow and outflow of fluids to the sensitive area of saidsensor chip.
 46. The applicator as claimed in claim 45, wherein saidfirst housing includes a gap filled with fluids during operation overthe sensitive area of said sensor chip and a ratio of a height of thegap to a largest diameter of the sensitive area of said sensor chip isless than 1 to
 5. 47. The applicator as claimed in claim 45, whereinsaid first housing includes a gap of less than 200 μm filled with fluidsduring functional operation over the sensitive area of said sensor chip.48. The applicator as claimed in claim 45, wherein said module and saidfirst housing are formed as a chip card with microfluidic components andfunctions integrated in therein.
 49. The applicator as claimed in claim45, wherein said sensor chip is provided with microfluidic componentsthat feed and carry away at least one of liquids and gases respectivelyto and from the sensitive area of said sensor chip.
 50. The applicatoras claimed in claim 45, further comprising storage for at least one ofsolids, liquids and gases.
 51. The applicator as claimed in claim 50,wherein said means for inflow and outflow of fluids include amicrofluidic connection between said storage and the sensitive area ofsaid sensor chip.
 52. The applicator as claimed in claim 51, whereinsaid first housing is a card having at least one layer.
 53. Theapplicator as claimed in claim 52, wherein said first housing is a cardmade of multiple materials.
 54. The applicator as claimed in claim 52,wherein said first housing further includes an integrated voltagesource, evaluation electronics and display.
 55. An analysis device,comprising: an applicator for decentralized measurements, including afirst housing having an interior and a surface, including a module,including a sensor chip having a sensitive area and electrical contacts;and a carrier having contact zones associated with the electricalcontacts of said sensor chip and an encapsulation with contactconnection between the contact zones and the electrical contacts of saidsensor chip to provide electrical access from outside said module, theencapsulation allowing access by a fluid to the sensitive area of saidsensor chip; and means for inflow and outflow of at least one of liquidsand gases to the sensitive area of said sensor chip via one of theinterior and on the surface of said first housing; and a second housing,including an evaluation unit, into which said applicator can beintroduced, to perform analysis and read out measurement data.
 56. Theanalysis device as claimed in claim 55, wherein said applicator is achip card; and wherein said second housing carries out the analysis andreads out the measurement data after said chip card is pushed into saidsecond housing.
 57. The analysis device as claimed in claim 56, whereinwhen said second housing carries out the analysis and reads out themeasurement data, at least one of liquids and gases are transferredbetween said applicator and said second housing.
 58. The analysis deviceas claimed in claim 55, wherein said first housing includes clearances,wherein the encapsulation includes an elastic material, and wherein saidsecond housing further comprises means for pressing the elasticencapsulation of said module against the clearances in said firsthousing.
 59. The analysis device as claimed in claim 58, furthercomprising temperature control means for setting a defined temperatureat the sensitive area of said sensor chip by cooling.
 60. The analysisdevice as claimed in claim 59, wherein said temperature control meanscomprises a Peltier element in said second housing for the sensor chip.61. The analysis device as claimed in claim 55, wherein the analysisdevice performs biochemical analytics.
 62. The analysis device asclaimed in claim 61, wherein the analysis device performs DNA analysis.63. The analysis device as claimed in claim 61, wherein the analysisdevice uses a Polymer Chain Reaction and said analysis device speedscooling during the Polymer Chain Reaction.
 64. The analysis device asclaimed in claim 55, wherein the analysis device performs foodmonitoring.
 65. The analysis device as claimed in claim 55, wherein theanalysis device performs environmental measuring.
 66. The analysisdevice as claimed in claim 55, wherein the analysis device performsforensics analysis.
 67. The analysis device as claimed in claim 55,wherein the analysis device performs medical diagnostics.
 68. Theanalysis device as claimed in claim 65, wherein the analysis deviceperforms blood gas/blood electrolyte analysis.